| Literature DB >> 29570999 |
Abhirup Das1, George X Huang2, Michael S Bonkowski3, Alban Longchamp4, Catherine Li5, Michael B Schultz3, Lynn-Jee Kim5, Brenna Osborne6, Sanket Joshi6, Yuancheng Lu3, Jose Humberto Treviño-Villarreal4, Myung-Jin Kang5, Tzong-Tyng Hung7, Brendan Lee7, Eric O Williams8, Masaki Igarashi8, James R Mitchell4, Lindsay E Wu5, Nigel Turner6, Zolt Arany9, Leonard Guarente10, David A Sinclair11.
Abstract
A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1-SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.Entities:
Keywords: NAD(+); aging; angiogenesis; endurance; exercise; hydrogen sulfide; ischemia; nicotinamide mononucleotide; sirtuins; skeletal muscle capillaries
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Year: 2018 PMID： 29570999 PMCID： PMC5884172 DOI： 10.1016/j.cell.2018.02.008
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582